The long-term objective of this study is to better understand the fate of inhaled particulate matter (PM) in the human lung. This is important whether PM exposure results from atmospheric pollution, biological warfare, and occupational factors or inhaled drug therapy. More and more evidence links the presence of fine PM in the air with cardiopulmonary diseases. This PM is of great concern because it can penetrate deep into the acinus. To date, the most realistic model of the human acinus consists of a multi-bifurcation structure of two-dimensional alveolated ducts (AD). In the present study we will develop three-dimensional acinar models of children and adult lung with a high degree of anatomical realism. A first type of model will consist of a single bifurcation of AD with rigid walls. A second type of model will address the effects of alveolar wall motions during breathing and will form a realistic structure of up to four successive bifurcations. This will be the most comprehensive acinar models yet developed. PM transport and deposition (DE) will be simulated for particle diameters (dp) ranging 0.005-5 (m and for flow rates ranging from quiet breathing to moderate exercise. For 0.5<dp<5 (m, DE is mainly due to gravitational sedimentation and is mainly affected by the structure orientation with respect to the gravity vector. For dp <0.5 (m, DE is mainly due to Brownian diffusion and is affected by the alveolar surface available to PM to deposit. The contribution of velocity profiles, rhythmical motions of the alveolar walls and PM intrinsic motions to overall convective mixing will be determined. Convective mixing causes inhaled PM to be irreversibly transferred to the resident air. As a result, some PM remains in suspension in the distal airways at the end of a normal expiration and penetrates deeper in the lung during the next breath where it eventually deposits. The process of stretch and fold where, because of non-reversibility of flow in the lung, air streamlines become folded back on themselves, will also be simulated to determine whether it is responsible for additional mixing in the acinus, and consequently for higher DE than that previously predicted. Finally the numerical predictions will be compared to experimental data obtained in human subjects and in simple physical models. The results of this study will provide a link to the mechanisms by which even seemingly modest PM exposure can cause or exacerbate lung disease and will also help to better design spatial targeting of inhaled drugs.